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Persons with Profound Intellectual and Multiple Disabilities (PIMD) are supported by professional caregivers for a large part of their lives. However, the perspectives of professional caregivers on good or poor Quality of Live (QoL) of persons with PIMD have hardly been explored. To explore the perspective of professional caregivers on QoL of persons with PIMD, we performed a qualitative study, conducting semi-structured interviews with eleven professional caregivers and thematically analysed them. In the interviews, these professional caregivers described examples of good and poor QoL. Good QoL was mostly described in emotional terms such as happiness, pleasure and enjoying things. Poor QoL was mostly described in physical terms such as pain, sickness and shortage of breath. The capability of persons with PIMD to influence the environment was described as an element of good QoL. Furthermore, these professional caregivers described how they assessed QoL. They 'sensed' QoL, they tested it (trial and error) and discussed QoL of persons with PIMD with colleagues. Participants emphasized the dependency of persons with PIMD on professional caregivers. Furthermore, these professional caregivers described feelings of failure and powerlessness if they could not assess or fulfil the needs of persons with PIMD. We conclude that these professional caregivers use their (tacit) knowledge to understand QoL of persons with PIMD. The relationship between QoL of persons with PIMD and professional caregivers needs more investigation, because of its consequences both for the persons with PIMD and the professional caregivers.

Study Question: What is the cost-effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) strategies from a societal perspective, when applying a time horizon of 1, 5 and 18 years?Summary Answer: From a short-term perspective (1 year) it is cost-effective to replace DET with single embryo transfer; however when intermediate- (5 years) and long-term (18 years) costs and consequences are incorporated, DET becomes the most cost-effective strategy, given a ceiling ratio of €20 000 per quality-adjusted life years (QALY) gained.What Is Already Known: According to previous cost-effectiveness research into embryo transfer strategies, DET is considered cost-effective if society is willing to pay around €20 000 for an extra live birth. However, interpretation of those studies is complicated, as those studies fail to incorporate long-term costs and outcomes and used live birth as a measure of effectiveness instead of QALYs. With this outcome, both multiple and singletons were valued as one live birth, whereas costs of all children of a multiple were incorporated.Study Design, Size, Duration: A Markov model (cycle length: 1 year; time horizon: 1, 5 and 18 years) was developed comparing a maximum of: (i) three cycles of eSET in all patients; (ii) four cycles of eSET in all patients; (iii) five cycles of eSET in all patients; (iv) three cycles of standard treatment policy (STP), i.e. eSET in women <38 years with a good quality embryo, and DET in all other women; and (v) three cycles of DET in all patients.Participants/materials, Setting, Methods: Expected life years (LYs), child QALYs and costs were estimated for all comparators. Input parameters were derived from a retrospective cohort study, in which hospital resource data were collected (n=580) and a parental questionnaire was sent out (431 respondents). Probabilistic sensitivity analysis (5000 iterations) was performed.Main Results and the Role Of Chance: With a time horizon of 18 years, DETx3 is most effective (0.54 live births, 10.2 LYs and 9.8 QALYs) and expensive (€37 871) per couple starting IVF. Three cycles of eSET are least effective (0.43 live births, 7.1 LYs and 6.8 QALYs) and expensive (€25 563). We assumed that society is willing to pay €20 000 per QALY gained. With a time horizon of 1 year, eSETx3 was the most cost-effective embryo transfer strategy with a probability of being cost-effective of 99.9%. With a time horizon of 5 or 18 years, DETx3 was most cost-effective, with probabilities of being cost-effective of 77.3 and 93.2%, respectively.Limitations, Reasons For Caution: This is the first study to use QALYs generated by the children in the economic evaluation of embryo transfer strategies. There remains some disagreement on whether QALYs generated by new life should be used in economic evaluations of fertility treatment. A further limitation is that treatment ends when it results in live birth and that only child QALYs were considered as measure of effectiveness. The results for the time horizon of 18 years might be less solid, as the data beyond the age of 8 years are based on extrapolation.Wider Implications Of the Findings: The current Markov model indicates that when child QALYs are used as measure of outcome it is not cost-effective on the long term to replace DET with single embryo transfer strategies. However, for a balanced approach, a family-planning perspective would be preferable, including additional treatment cycles for couples who wish to have another child. Furthermore, the analysis should be extended to include QALYs of family members.Study Funding/competing Interests: This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Assessing Quality of Life (QoL) of persons with profound intellectual and multiple disabilities (PIMD) is challenging, yet QoL plays an important role in medical decision-making processes concerning persons with PIMD. The perspectives of parents of children with PIMD on the assessment of their QoL have not been studied., Aim: To explore the perspectives of parents on the assessment of QoL of their children., Methods: We conducted a qualitative study, forming three focus groups with 22 parents of children with PIMD to explore their views on what is necessary to assess QoL of their children and subsequently, who is best suited to assess QoL., Results: Parents describe a long-term relationship of the assessor with family (child and parents), with trust as an important aspect, as a requirement to assess QoL. Parents consider family members, preferably the parents themselves as the best assessors of QoL, followed by siblings. Professional caregivers, mostly mentioned by name, are considered the next alternative. Most parents thought that physicians do not know the child well enough to assess their QoL., Conclusions: In conclusion, the parents of children with PIMD in our study consider trust and a long-term relationship essential for assessing QoL., Competing Interests: Disclosure statement The authors declare that they have no conflicts of interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Maternal stress in the postpartum period affects not only the mother, but also her newborn child who is at increased risk for a wide range of disorders later in life. The mechanisms underlying transmission of maternal stress to the child remain elusive. Human milk (HM) is a potential candidate and is an important source of fatty acid (FA), which are crucial for child (neuro)development. This study aims to investigate whether maternal psychological and biological stress influences HM FA composition over the first month postpartum., Methods: The Amsterdam Mother's Milk study is a prospective cohort study. We included lactating women who delivered at term with a large range of stress levels: a high stress (HS) group, women whose child was hospitalized for a minimum of 2 days (n=23) and a control (CTL) group, women who gave birth to a healthy child (n=73). HM was collected three times a day at postpartum days 10, 17 and 24. Perceived psychological stress was measured using multiple validated questionnaires, while biological stress measures were based on cortisol in hair, saliva and HM. HM FAs were analyzed by gas-chromatography and compared between groups., Results: Maternal perceived stress scores were significantly higher in the HS group (p < 0.01), whereas cortisol measurements did not differ between groups. The absolute concentrations of total FA in HM (p=0.023), including the total amount of poly unsaturated fatty acids (PUFAs) (p=0.022) and omega-6 PUFAs (p=0.018), were lower in the HS group compared to the CTL group. Relative values of FAs did not differ between groups., Conclusion: Maternal stress in the first month postpartum was associated with overall lower levels of FA in HM. This possibly indicates a route of transmission of maternal stress signals to the infant. Future research should investigate if these stress-induced changes in HM FAs have consequences for child development., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8 + T cells are critical to achieve viral control. However, studies investigating the development of CD8 + T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8 + T cell compartment in human fetal, infant and adult intestinal tissues. CD8 + T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7 - CD45RA - CD127 - KLRG1 +/- CD8 + T cells compared to tissue-resident memory CD69 + CD103 + CD8 + T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8 + T cells was, however, markedly reduced compared to adult intestinal CD8 + T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8 + T cells. Taken together, we demonstrate that intestinal CD8 + T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8 + T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

The aim of this study was to determine the potential impact of the Pediatric Emergency Care Applied Research Network (PECARN) rules on the CT rate in a large paediatric minor traumatic head injury (MTHI) cohort and compare this with current national Dutch guidelines. This was a planned sub-study of a prospective multicentre observational study that enrolled 1006 children younger than 18 years with MTHI. We calculated the number of recommended CT scans and described trauma-related CT scan abnormalities. The PECARN rules recommended a significantly lower percentage of CT scans in all age categories, namely 101/357 (28.3%) versus 164/357 (45.9%) (p < 0.001) in patients under 2 years of age and 148/623 (23.8%) versus 394/623 (63.2%) (p < 0,001) versus in patients 2 years and older.Conclusion: The projected CT rate can significantly be reduced if the PECARN rules are applied. We therefore advocate that the PECARN guidelines are also implemented in The Netherlands. What is Known: • To guide clinicians whether to perform a CT scan in children with a minor traumatic head injury (MTHI) clinical decision rules has been developed. • The overall CT scan rate in adherence with the Dutch MTHI guidelines is 44%. What is New: • The projected CT rate can significantly be reduced in a Dutch cohort of MTHI if the PECARN rules are applied. • The Dutch national guidelines for MTHI can safely be replaced by the PECARN rules.

Background & Aims: Maternal obesity at conception is considered a major predictor of offspring obesity. This could by driven at least in part by an altered placental fat transfer. However, the pathophysiological mechanisms involved are not fully understood. We investigated the in vivo materno-fetal transfer of fatty acids (FAs) in obese pregnant women using stable isotopes., Methods: Ten obese and ten normo-weight pregnant women (control) received orally a bolus of 13 C-labeled FAs 12 h before elective caesarean section: oleic acid ( 13 C-OA), linoleic acid ( 13 C-LA) and docosahexaenoic acid ( 13 C-DHA). Maternal blood samples were collected at -12 (basal), -8, -4, -2, 0 h relative to the time of cesarean section. At the time of birth, arterial and venous cord bloods as well as placental tissue were collected. FAs composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry., Results: Maternal plasma insulin and placental weight tended to higher values in obese pregnant women although they did not present serum hyperlipidemia. Higher concentrations of 13 C-LA and 13 C-DHA were found in non-esterified FAs fraction in maternal plasma of obese mothers. The ratio of placental uptake for 13 C-LA and 13 C-DHA was lower in obese women compared to normal weight pointing toward a limited capacity of FA placental transfer, especially of essential FAs. Maternal insulin was associated to this lower placenta/maternal plasma ratio for both 13 C-LA (R = -0.563, P = 0.012) and 13 C-DHA (R = -0.478, P = 0.033). In addition, the ratio cord/maternal plasma of 13 C-LA was significantly lower in obese women compared to controls., Conclusions: In conclusion, obese mothers without hyperlipidemia showed a reduced materno-fetal transfer of polyunsaturated FAs which could affect fetal development. This affect dietary recommendation for obese pregnant women., Trial Registry Number: ISRCTN69794527., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Persons with Profound Intellectual and Multiple Disabilities (PIMD) are supported by professional caregivers for a large part of their lives. However, the perspectives of professional caregivers on good or poor Quality of Live (QoL) of persons with PIMD have hardly been explored. To explore the perspective of professional caregivers on QoL of persons with PIMD, we performed a qualitative study, conducting semi-structured interviews with eleven professional caregivers and thematically analysed them. In the interviews, these professional caregivers described examples of good and poor QoL. Good QoL was mostly described in emotional terms such as happiness, pleasure and enjoying things. Poor QoL was mostly described in physical terms such as pain, sickness and shortage of breath. The capability of persons with PIMD to influence the environment was described as an element of good QoL. Furthermore, these professional caregivers described how they assessed QoL. They 'sensed' QoL, they tested it (trial and error) and discussed QoL of persons with PIMD with colleagues. Participants emphasized the dependency of persons with PIMD on professional caregivers. Furthermore, these professional caregivers described feelings of failure and powerlessness if they could not assess or fulfil the needs of persons with PIMD. We conclude that these professional caregivers use their (tacit) knowledge to understand QoL of persons with PIMD. The relationship between QoL of persons with PIMD and professional caregivers needs more investigation, because of its consequences both for the persons with PIMD and the professional caregivers., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period., Objective: To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14days after birth was associated with improvement in length and bone development until 9-10years of age., Design: Observational follow-up study of VLBW infants (birth weight<1500g or gestational age<32weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intake and clinical covariates on length and bone mineralization., Results: Both cohorts achieved a catch-up in length to SDS within the normal range by 6months (length SDS: estimated mean (95% confidence interval (CI): 6months: Cohort 2004: -0.7 (-1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: β 0.001; 95% CI (0.000, 0.003); p=0.03) There was no evidence of an association between early nutritional intake and bone mineralization., Conclusion: Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14days after birth was not associated with improvement in length and bone development., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: End-of-life decisions (EoLDs) are very difficult to make. How parents and physicians incorporate quality of life (QoL) considerations into their end-of-life decision making (EoLDM) for children with profound intellectual and multiple disabilities (PIMD) remains unknown., Aims: To determine which elements contribute to QoL according to parents and physicians, how QoL is incorporated into EoLDM and how parents and physicians discuss QoL considerations in the Netherlands., Methods: Semi-structured interviews were conducted with the physicians and parents of 14 children with PIMD for whom an EoLD had been made within the past two years., Results: Parents and physicians agreed on the main elements that contribute to QoL in children with PIMD. The way in which QoL was incorporated differed slightly for different types of decisions. Parents and physicians rarely discussed elements contributing to the child's QoL when making EoLDS., Conclusions: and Implications Although QoL was highly important during EoLDM for children with PIMD, parents and physicians did not fully explore the elements that contribute to the child's QoL when they made EoLDs. We recommend the development of a communication tool that will help parents and physicians discuss elements that contribute to QoL and the consequences these elements have for upcoming decisions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Studies on immune cells derived from the human intestine are needed to understand the pathogenesis of gastrointestinal diseases and to develop novel treatment strategies. Isolation techniques to extract these immune cells from intestinal tissue are largely based on murine studies and comparative data on isolation from human intestine is scarce. In this study we evaluated cell yield, viability, and surface-molecule expression on mononuclear leukocytes, comparing three techniques to obtain a single immune cell suspension from human intestine; low concentrations of either the enzymes Collagenase D or Liberase TL, and enzyme-free mechanical dissociation with the Medimachine. Both enzymatic isolation techniques provided a higher cell yield than mechanical dissociation. Expression of surface molecules remained intact after Collagenase D treatment, while Liberase TL digestion resulted in a strong decrease in the expression of the CD4 receptor. Taken together, Collagenase D digestion provides the highest yield of mononuclear cells while keeping surface molecule expression intact., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: End-of-life decisions (EoLD) often concern children with profound intellectual and multiple disabilities (PIMD). Yet, little is known about how parents and physicians discuss and make these decisions., Aims: The objective of this research was to investigate the experiences of the parents and the involved physician during the end-of-life decision-making (EoLDM) process for children with PIMD., Methods: In a retrospective, qualitative study, we conducted semi-structured interviews with the physicians and parents of 14 children with PIMD for whom an EoLD was made within the past two years., Results: A long-lasting relationship appeared to facilitate the EoLDM process, although previous negative healthcare encounters could also lead to distrust. Parents and physicians encountered disagreements during the EoLDM process, but these disagreements could also improve the decision-making process. Most parents, as well as most physicians, considered the parents to be the experts on their child. In making an EoLD, both parents and physicians preferred a shared decision-making approach, although they differed in what they actually meant by this concept., Conclusion: The EoLDM process for children with PIMD can be improved if physicians are more aware of the specific situation and of the roles and expectations of the parents of children with PIMD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Aims: The objectives of this integrative review were to understand how parents of children with severe developmental disorders experience their involvement in end-of-life decision-making, how they prefer to be involved and what factors influence their decisions., Methods and Procedures: We searched MEDLINE, EMBASE, CINAHL and PsycINFO. The search was limited to articles in English or Dutch published between January 2004 and August 2014. We included qualitative and quantitative original studies that directly investigated the experiences of parents of children aged 0-18 years with severe developmental disorders for whom an end-of-life decision had been considered or made., Outcomes and Results: We identified nine studies that met all inclusion criteria. Reportedly, parental involvement in end-of-life decision-making varied widely, ranging from having no involvement to being the sole decision-maker. Most parents preferred to actively share in the decision-making process regardless of their child's specific diagnosis or comorbidity. The main factors that influenced parents in their decision-making were: their strong urge to advocate for their child's best interests and to make the best (possible) decision. In addition, parents felt influenced by their child's visible suffering, remaining quality of life and the will they perceived in their child to survive., Conclusions and Implications: Most parents of children with severe developmental disorders wish to actively share in the end-of-life decision-making process. An important emerging factor in this process is the parents' feeling that they have to stand up for their child's interests in conversations with the medical team., (Copyright © 2015 Elsevier Ltd. All rights reserved.)